Objectives: American shad (Alosa sapidissima) is an important migratory fish under Alosine and has long been valued for its economic, nutritional and cultural attributes. Overfishing and barriers across the passage made it vulnerable to sustain. To protect this valuable species, aquaculture action plans have been taken though there are no published genetic resources prevailing yet. So, here we reported a de novo transcriptome assembly and annotation for A. sapidissima from blood and brain tissues for the first time.Data description: We generated 160,481 and 129,040 non-redundant transcripts from brain and blood tissues. The entire work strategy involved RNA extraction, library preparation, sequencing, de novo assembly, filtering, annotation and validation. Both coding and non-coding transcripts were annotated against Swissprot and Pfam datasets. Nearly, 83% coding transcripts were functionally assigned. Protein clustering with clupeiform and non-clupeiform taxa revealed ~82% coding transcripts retained the orthologue relationship which improved confidence over annotation procedure. Hopefully, it can serve as an useful resource in future for the research community to elucidate molecular mechanisms for several key traits like migration which is fascinating in clupeiform shads.